Non-invasive brain stimulation as a tool to decrease chronic pain in current opiate users: A parametric evaluation of two promising cortical targets

Drug Alcohol Depend. 2021 Jan 1:218:108409. doi: 10.1016/j.drugalcdep.2020.108409. Epub 2020 Nov 23.


Background: Poorly controlled chronic pain can lead to non-prescription use of opiates, which is a growing crisis in our communities. Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic tool which has emerged as a potential treatment option for these patients. It is still unclear, however, if the dorsolateral prefrontal cortex (DLPFC) or the motor cortex (MC) is a more effective treatment location. The purpose of this study was to directly compare the effects of DLPFC versus MC TMS on pain severity and the urge to use opiates among chronic pain patients.

Methods: Twenty-two individuals with chronic pain currently using prescription opiates were randomized to receive 10, 3000 pulse sessions of 10 Hz repetitive TMS (rTMS) to the left DLPFC (110% resting motor threshold) or left MC (90% resting motor threshold). Multivariate linear models were used to evaluate the effect of TMS on pain and opiate use, including items from the Brief Pain Inventory (BPI) as well as subjective ratings of pain, distress, and the urge for opiates.

Results: Twenty participants (91%) completed all 10 treatment sessions and follow up visits. There was a main effect of stimulation site (F7,210 = 3.742, p = 0.001), wherein MC stimulation decreased pain interference significantly more than DLPFC stimulation (F1,216 = 8.447, p = 0.004). While both sites had comparable effect sizes on stress, pain, and discomfort, MC stimulation had larger effects on pain interference (Cohen's d: 0.7) and urge to use opiates (Cohen's d: 0.5) than DLPFC stimulation.

Conclusion: These data suggest that the MC may be a promising target for decreasing opiate dependence and pain interference among chronic pain patients.

Keywords: Neuromodulation; Opiates; Pain; Transcranial magnetic stimulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Analgesics, Opioid
  • Chronic Pain / etiology
  • Chronic Pain / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex
  • Opiate Alkaloids
  • Opioid-Related Disorders / therapy*
  • Pain Measurement
  • Prefrontal Cortex / physiology
  • Rest
  • Transcranial Magnetic Stimulation*
  • Treatment Outcome


  • Analgesics, Opioid
  • Opiate Alkaloids